Healthy Siblings Research Articles

A Multicenter Network Analysis Examining the Psychological Effects of the COVID-19 Pandemic on Patients with Eating Disorders versus Their Healthy Siblings.

(1) Background: The impact of the COVID-19 pandemic on individuals with eating disorders (EDs) has been recorded all over the world; the traumatic effects of COVID-19 have exacerbated specific and general psychopathologies in those with EDs. Comparing patients' and their healthy siblings' responses might help one evaluate whether there are significant differences between healthy individuals and those struggling with EDs in regard to posttraumatic psychological symptoms. (2) Methods: A sample of 141 ED patients and 99 healthy siblings were enrolled in this study in two different centers specializing in ED treatment. All participants completed the posttraumatic stress disorder (PTSD) checklist and an eating and general psychopathological self-report questionnaire. Network analysis was then applied to evaluate the differences between the populations. (3) Results: No significant differences emerged between the network structures despite the significant differences between patients and their healthy siblings in regard to posttraumatic symptoms, eating, and general psychopathology. (4) Conclusion: The complex nature of the interaction between environmental and personal factors should be evaluated further in individuals with EDs due to how they respond to traumatic events, which exacerbate patients' psychopathology.

Effects of Sensory Integration Therapy with Sibling on Peer Interactions among Children with Disabilities

This study aimed to evaluate the effects of applying sensory integration therapy on the peer interaction of siblings with children with disabilities. These subjects were preschool children aged between 3 and 7 years who had used the child development center. A total of 20 children were recruited, 10 for the experimental and control groups. Then, 10 healthy siblings of children with disability supported the experimental group and compared with the control group. The sibling sensory integration therapy was performed in the experimental group, whereas individual sensory integration therapy was conducted in the control group. The treatment was administered once a week for a total of 10 weeks, 40 min per session, and 10-min interview with the children's parents. Based on the theory of sensory integration therapy, play that meets the neurological needs of each child was selected and provided. The total score is 0-96 points, indicating that the higher the score, the more negative peer interactions, and that the lower the score, the more positive the peer interactions. Among them, 22–29 and 31 questions were scored in reverse because they meant that the lower the score, the more negative the interactions. This tool is divided into three subcategories: play disruption (13 questions), disconnection (11 questions), and interaction (8 questions). A significant difference was confirmed in the area of play disruption in the experimental group and total scores; however, no significant difference was observed in the other areas. When sensory integration therapy intervention was applied to children with disability and their siblings, it was more effective within the play disruption area of peer interaction than in children with disability without a sibling.

Age-related trajectories of DNA methylation network markers: A parenclitic network approach to a family-based cohort of patients with Down Syndrome

Despite the fact that the cause of Down Syndrome (DS) is well established, the underlying molecular mechanisms that contribute to the syndrome and the phenotype of accelerated aging remain largely unknown. DNA methylation profiles are largely altered in DS, but it remains unclear how different methylation regions and probes are structured into a network of interactions. We develop and generalize the Parenclitic Networks approach that enables finding correlations between distant CpG probes (which are not pronounced as stand-alone biomarkers) and quantifies hidden network changes in DNA methylation. DS and a family-based cohort (including healthy siblings and mothers of persons with DS) are used as a case study. Following this approach, we constructed parenclitic networks and obtained different signatures that indicate (i) differences between individuals with DS and healthy individuals; (ii) differences between young and old healthy individuals; (iii) differences between DS individuals and their age-matched siblings, and (iv) difference between DS and the adult population (their mothers). The Gene Ontology analysis showed that the CpG network approach is more powerful than the single CpG approach in identifying biological processes related to DS phenotype. This includes the processes occurring in the central nervous system, skeletal muscles, disorders in carbohydrate metabolism, cardiopathology, and oncogenes. Our open-source software implementation is accessible to all researchers. The software includes a complete workflow, which can be used to construct Parenclitic Networks with any machine learning algorithm as a kernel to build edges. We anticipate a broad applicability of the approach to other diseases.

NCOG-45. DIFFERENTIAL AND DOSE-DEPENDENT EFFECTS OF CRANIAL IRRADIATION ON BRAIN STRUCTURES AND NEUROPSYCHOLOGICAL OUTCOMES IN CHILDREN WITH POSTERIOR FOSSA BRAIN TUMORS TREATED WITH DIFFERENT MODALITIES

Abstract BACKGROUND Studies investigating dose-dependent effects of cranial irradiation (CRT) in children with posterior fossa brain tumors are limited by examining combined effects of surgery, chemotherapy, and radiation. We aimed to determine alterations in brain volume and microstructure, and neuropsychological outcomes in children with posterior fossa tumors treated with surgery alone, surgery and chemotherapy, and surgery, chemotherapy, and CRT combined. We explored the relationship of radiation dose to the thalamus, putamen, and hippocampus to outcomes of intelligence, processing speed, executive functions, memory, and social/emotional functioning. METHODS Forty-seven children with treated posterior fossa tumors (17 with surgery; 11 with surgery and chemotherapy; 19 with surgery, chemotherapy, and CRT) underwent neuroimaging and neuropsychological assessment a mean of 4.8 years after treatment, along with 17 healthy sibling controls (n=64). The putamen, thalamus and hippocampus were manually segmented on MRI, and structural mean radiation doses were calculated. Differences in demographics and medical history were evaluated using χ2 and t-tests. Linear regression examined differences in neuropsychological performance, structural volumes, and diffusion indices. Pearson correlation explored relationships of structural radiation doses to diffusion indices and neuropsychological outcomes. RESULTS All patients scored lower on Block Design than controls (p=0.01), and the surgery and chemotherapy group scored the lowest. There was no significant difference in mean fractional anisotropy (FA) values in the thalamus, hippocampus and putamen between the three patient groups and controls. Hippocampal volume and mean radiation dose approached significant correlation (r= -0.49; p=0.07). Right putamen FA correlated with mean radiation dose (r=0.56; p=0.02). When controlling for age, thalamic volume was lowest in the irradiated group (p=0.02). CONCLUSIONS Treatment of pediatric posterior fossa brain tumors with surgery, chemotherapy, and CRT impacts thalamic volume and may have a dose-dependent effect on the microstructure of the putamen compared to treatment with surgery/chemotherapy.

Transcriptomic analysis reveals an association of FCGBP with Parkinson’s disease

Transcriptomics in Parkinson’s disease (PD) offers new insights into the molecular mechanism of PD pathogenesis. Several pathways, such as inflammation and protein degradation, have been identified by differential gene expression analysis. Our aim was to identify gene expression differences underlying the disease etiology and the discovery of pre-symptomatic risk biomarkers for PD from a multicenter study in the context of the PROPAG-AGEING project. We performed RNA sequencing from 47 patients with de novo PD, 10 centenarians, and 65 healthy controls. Using identified differentially expressed genes, functional annotations were assigned using gene ontology to unveil significant enriched biological processes. The expression of 16 selected genes was validated using OpenArray® assays and samples from independent cohorts of 201 patients with advanced PD, 340 healthy siblings of PD patients, and 177 healthy controls. Differential gene expression analysis identified higher FCGBP expression in patients with de novo PD compared with healthy controls and compared with centenarians. Furthermore, FCGBP showed no differences in terms of population origin or aging process. The increased FCGBP expression was validated in patients with advanced PD and their siblings. Thus, we provided evidence for an upregulation of FCGBP mRNA levels not only in patients with PD but also in individuals at putative higher risk of PD, suggesting that it could be important in gut–brain PD interaction, mediating the connection between microbiota and intestinal inflammatory processes, as well as neuroinflammation and neurodegeneration.

The correlation between copy number variation in Chromosome 14 and DNA methylation in Saudi autistic children.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that represents a range of aberrant behaviour symptoms such as repetitive behaviours and defects in social communication. The prevalence of ASD has been increasing worldwide and many studies have reported that both genetic and epigenetic factors play an important role in the etiology of this disorder. The aim of this study was to investigate the implementation of DNA methylation and Copy number variation (CNV) in the diagnosis of ASD. This study was carried out on 14 Saudi autistic children and four of their healthy siblings. Comparative genomic hybridization array was used to identify CNV in chromosome 14 and MethyLight qPCR was used to estimate levels of DNA methylation. The results identified CNVs in six cytobands in chromosome 14 for 13 out of 14 autistic samples: 14q11.1-q11.2, 14q11.2, 14q12, 14q21.1, 14q32.2, and 14q32.33. However, some of these cytobands were also found in normal samples with different sizes. Interestingly, chromosomal abnormalities in 14q11.1-q11.2 was only found in ASD samples. The result also showed an increase in methylation ratio of ASD samples in those CNV regions compared with their siblings. The findings suggest that CNV in 14q11.1-q11.2 might be a potential target in ASD diagnosis and further work is required to detect which biological pathways are affected.

Comparison of psychosocial adaptations among childhood cancer survivors, their siblings and peers in Taiwan

PurposeThis study aimed to understand the difference in psychosocial adaptation among childhood cancer survivors, their healthy siblings and peers, and the factors affecting the psychosocial adaptation of these cancer survivors. Design and methodsA total of 222 children (ages 8–17) including childhood cancer survivors, their siblings, and healthy peers participated in this cross-sectional study. All the children completed the anxiety and quality of life scales for their age groups. ResultsAnxiety levels and quality of life were similar among the childhood cancer survivors, their siblings, and their peers. The anxiety of elementary school-age survivors of acute leukemia was higher than that of those with solid tumors. Elementary school-age survivors who completed three or more years of treatment had lower anxiety than those who completed treatment within the three years. For adolescent survivors, the higher their body mass index, the higher their anxiety, which was associated with low quality of life. Those diagnosed with anxiety and at an older age had lower quality of life. ConclusionsAlthough there were no differences in survivors' psychosocial adaptation compared to their siblings and healthy peers, more than half of these adolescents had moderate to severe anxiety. Future study may need to explore the causes of their anxiety. Practice implicationsDuring the follow-ups of the childhood cancer survivors, age-specific adaptive strategies can be discussed to reduce their anxiety and improve their quality of life.

Sequence variants in the ITGB2 gene underlying leukocyte adhesion deficiency Type-1 in four consanguineous families

Integrins are integral transmembrane proteins involved in various biological activities. One such protein β2 integrin CD18, encoded by ITGB2 gene, is involved in leukocyte adhesion and wound healing. Leukocyte adhesion and crawling being the key process in combating infections are mainly facilitated by β2 integrins. Sequence variants in the ITGB2 gene cause leukocyte adhesion deficiency, type I (LAD1). To search for the disease-causing sequence variants in four patients with LAD1 born to four different consanguineous parents of Pakistani origin. Flow cytometry was used to measure CD18 levels. Genomic DNA was extracted from the blood of the patients, parents, and healthy siblings. Using exon-specific primers, the ITGB2 gene was Sanger sequenced. Clinical features including skin abscesses, delayed umbilical cord separation, mild omphalitis, and neutrophilia were recorded in the patients. Flow-cytometric analysis revealed highly reduced CD18 levels (< 2 %) in the patients. Sequence analysis of the ITGB2 gene revealed four disease-causing variants, including two novels [p.(Tyr130*), p.(Ala245Pro)], and two previously reported [p. (Cys62*), p.(Asp128Tyr)]. Identification of the LAD1 causative variants further expanded the mutation spectrum in the ITGB2 gene. This study will facilitate genetic counseling of the families carrying LAD1 type features in the Pakistani population.

Language and developmental plasticity after perinatal stroke

The mature human brain is lateralized for language, with the left hemisphere (LH) primarily responsible for sentence processing and the right hemisphere (RH) primarily responsible for processing suprasegmental aspects of language such as vocal emotion. However, it has long been hypothesized that in early life there is plasticity for language, allowing young children to acquire language in other cortical regions when LH areas are damaged. If true, what are the constraints on functional reorganization? Which areas of the brain can acquire language, and what happens to the functions these regions ordinarily perform? We address these questions by examining long-term outcomes in adolescents and young adults who, as infants, had a perinatal arterial ischemic stroke to the LH areas ordinarily subserving sentence processing. We compared them with their healthy age-matched siblings. All participants were tested on a battery of behavioral and functional imaging tasks. While stroke participants were impaired in some nonlinguistic cognitive abilities, their processing of sentences and of vocal emotion was normal and equal to that of their healthy siblings. In almost all, these abilities have both developed in the healthy RH. Our results provide insights into the remarkable ability of the young brain to reorganize language. Reorganization is highly constrained, with sentence processing almost always in the RH frontotemporal regions homotopic to their location in the healthy brain. This activation is somewhat segregated from RH emotion processing, suggesting that the two functions perform best when each has its own neural territory.

When lightning strikes twice: Perceptions of oncology social workers about working with families with two members in treatment.

Families with a parent and child concurrently receiving cancer treatment are not common, but their needs are typically more complex than families with only one member in treatment. They have a heightened sense of loss, vulnerability, and mortality. The study purpose was to: (1) describe quality of life, social support, resiliency, and loss for these families; and (2) describe how healthcare teams can support these families. This was a qualitative study with 20 oncology social workers who had worked with families with a parent and child concurrently receiving treatment for cancer within the past five years. The interview included questions about the emotional, social, financial, and other needs of these families, as well as their social support, quality of life, loss, and resiliency. Three themes emerged from the data: 1. Increased demands on the family with a concurrent cancer treatment, including emotional, financial, and logistical challenges for the ill parent and child and for the healthy parent and siblings; 2. Greater resilience and coping skills were experienced by some families; and 3. Implications for the healthcare team, including emotional distress in treating these families, challenges in treatment adherence, and providing the necessary support to these families. Supporting these families is challenging for social workers and other members of the healthcare team. Understanding the emotional, financial and logistical needs of these families, and coordinating their care across the adult and pediatric teams, will better support the patients, as well as the healthcare providers who work with them.

Can the Imbalance between Neurotrophic and Apoptotic Proteins Be the "Beware the Ides of March" for Unaffected Relatives of Schizophrenia Patients?

Schizophrenia (SZ) is a mental disorder with a strong genetic basis as well as epigenetic aspects. Siblings of patients with SZ can share certain endophenotypes with the patients, suggesting that siblings may be important for distinguishing between trait and state markers. In the current study, we aimed to characterize the balance between pro-BDNF/mature BDNF and its receptors p75NTR/TrkB, which are tPA-BDNF pathways proteins and arethought to play a role in synaptic pruning,as a possible endophenotype of schizophrenia. Forty drug-naïve patients with first-episode psychosis (FEP) matched for age, gender, and level of education, 40 unaffected siblings (UAS) of patients with FEP, and 67 healthy controls (HC) were included in the study. Blood samples were collected from all participants to determine BDNF, pro-BDNF, TrkB and p75NTR, PAI1, tPA, ACTH, and cortisol levels. We showed that levels of proteins of the tPA-BDNF pathway as well as the pro-BDNF/m-BDNF and p75NTR/TrkB ratios could successfully differentiate FEP and their siblings from the HCs by using ROC analysis. Plasma levels of m-BDNF were found to be the lowest in the healthy siblings and highest in the HCs with statistically significant differences between all 3 groups. The plasma level of pro-BDNF in the HC group was similar to the FEP patients, the same in the healthy siblings of the FEP patients. Our data support the hypothesis that imbalance between neurotrophic and apoptotic proteins might occur in SZ and this imbalance could be an endophenotype of the disease.

Global longitudinal strain assessment in long-term survivors of childhood acute lymphoblastic leukemia

Abstract Background The role of global longitudinal strain (GLS) in the long-term cardiac evaluation of childhood acute lymphoblastic leukemia (ALL) survivors is not clearly defined. Purpose To assess the prevalence of subclinical left ventricular systolic dysfunction (SLVD) in long-term survivors of ALL. We also aimed to compare echocardiographic measurements with a control group. Methods Patients &amp;lt;18 years of age diagnosed with ALL between 1985–2015 at our center were enrolled. Healthy siblings willing to participate were conformed the control group. GLS was measured with an automated software (AutoStrain, Tomtec). SLVD was defined as GLS&amp;lt;18.5% (absolute value) based on the lower limit of the 95% confidence interval in the control group. Group differences were accounted with nverse probability of treatment weighting. Results Of the 90 survivors included (37.8% female, time from diagnosis 18 [11–26] years), 24 (26.6%) had SLVD. Left ventricular systolic but not diastolic measurements were reduced compared to the control group (Table 1). Predictors of GLS in the survivors were smoking (p=0.004) and history of hematopoietic stem-cell transplantation (p=0.042) (Table 2). Conclusions Over ¼ of childhood ALL survivors had abnormal GLS values after a median follow-up of 18 years. Left-ventricular systolic parameters were reduced compared to a control group. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Sociedad Española de Cardiología. Sociedad Andaluza de Cardiología.

An expansion of phenotype: novel homozygous variant in the MED17 identified in patients with progressive microcephaly and global developmental delay

Global developmental delay (GDD) is a lifelong disability that affects 1–3% of the population around the globe. It is phenotypically variable and highly heterogeneous in terms of the underlying genetics. Patients with GDD are intellectually disabled (ID) manifesting cognitive impairment and deficient adaptive behavior. Here, we investigated a two-looped consanguineous family segregating severe ID, seizure, and progressive microcephaly. Magnetic resonance imaging (MRI) of the brain showed mild brain atrophy and myelination defect. Whole exome sequencing (WES) was performed on the DNA samples of two patients and a novel homozygous missense variant (Chr11:g0.93528085; NM_004268.5_c.871T > C; p. Trp291Gly) was identified in the MED17 gene. Sanger sequencing revealed that the identified variant is heterozygous in both parents and healthy siblings. This variant is conserved among different species, causes a non-conserved amino acid change, and is predicted deleterious by various in silico tools. The variant is not reported in population variant databases. MED17 (OMIM: 613668) encodes for the mediator of RNA polymerase II transcription complex subunit 17. Structure modeling of MED17 protein revealed that Trp291 is involved in different inter-helical interactions, providing structural stability. Replacement of Trp291Gly, a less hydrophobic amino acid loses the inter-helical interaction leading to a perturb variant of MED17 protein.

GRISCELLI SYNDROME TYPE 2 –CLINICAL APPROACH AND CASE REPORT

Griscelli syndrome type 2 is rare authosomal ressesive disorder caused by a defect in the RAB27A gene, which affects a melanosome-anchoring complex in melanocytes, affecting release of cytolytic granules from T and NK cells. Children with GS type 2 develop an uncontrolled T-lymphocyte and macrophage activation syndrome known as hemophagocytic syndrome (HS) or hemophagocytic lymphohistiocytosis (HLH). We describe a 3 years old girl patient classic features of Griscelli syndrome type 2 A 3-year-old girl was admitted to hematology with complaints of LAP, hepatosplenomegaly and pancytopenia (WBC- 3080/µl, Hb-7.6 g/dl, Neutr.-350/µl, PLT - 165000/µl). The patient's condition was below the percentile, her skin was bronze, her hair was silver-grey. HLH criteria were met (triglycerides 458 mg/mL, ferritin 3445 ng/mL, fibrinogen 180 mg/dl). Morphology of the bone marrow was hypocellular, signs of dyserythropoiesis (stage I) and megakaryocytes were reduced According to the clinical and laboratory data(hepatosplenomegaly, increased ferritin, hypertriglyceridemia, pancytopenia, hyperthermia resistant to antimicrobial therapy, silver-gray hair, pigment balls of hair seen light microscope) and the death of another undiagnosed child in the family, suggested likely primary HLH and GS. As a result of genetic analysis (homozygous mutation c.514_ 518delCAAGC(p.GLN172Asnfs*,rs767481076)1 in the RAB27A gene), the diagnosis of GS type 2 was confirmed. The patient was treated according to the HLH 2004 protocol. CSA levels were measured once a week. IVIG support was given based on IgG levels. HSCT was planned from patient's healthy HLA-matched sibling, but HSCT was delayed because the brother was infant. After 45 weeks of maintenance therapy, etoposide was discontinued, dose of dexamethasone was reduced to 5 mg/kg, but CSA was continued at the same dose. Control studies are carried out once a week. As far as possible HSCT is planning The prognosis of patients with Griscelli syndrome is poor. It is usually rapidly fatal within 1-4 years without aggressive treatment and bone marrow transplantation at onset of an accelerated phase. HSCT is more successful when implemented early course of the disease. Palliative care includes treatment and prophylaxis care infections and immunosupressor therapy in accelerated phases. Some patients have died after transplantation, but others have had lasting remissions

Microbial gut evaluation in an angolan paediatric population with sickle cell disease.

Sickle cell disease (SCD) is one of the most common genetic conditions worldwide. It can contribute up to 90% of under-5 mortality in sub-Saharan Africa. Clinical manifestations are very heterogeneous, and the intestinal microbiome appears to be crucial in the modulation of inflammation, cell adhesion and induction of aged neutrophils, the main interveners of recurrent vaso-occlusive crisis. Enterocyte injury, increased permeability, altered microbial composition and bacterial overgrowth have all been documented as microbial and pathophysiologic changes in the gut microbiome of SCD patients in recent studies. Our aim was to sequence the bacterial 16S rRNA gene in order to characterize the gut microbiome of Angolan children with SCA and healthy siblings as a control. A total of 72 stool samples were obtained from children between 3 and 14 years old. Our data showed that the two groups exhibit some notable differences in microbiota relative abundance at different classification levels. Children with SCA have a higher number of the phylum Actinobacteria. As for the genus level, Clostridium cluster XI bacteria was more prevalent in the SCA children, whereas the siblings had a higher abundance of Blautia, Aestuariispira, Campylobacter, Helicobacter, Polaribacter and Anaerorhabdus. In this study, we have presented the first microbiota analysis in an Angolan paediatric population with SCD and provided a detailed view of the microbial differences between patients and healthy controls. There is still much to learn before fully relying on the therapeutic approaches for gut modulation, which is why more research in this field is crucial to making this a reality.

Mental health of siblings of children with physical illness or physical-mental comorbidity.

This study examined the mental health of siblings of children with physical illness (PI), with or without co-occurring mental illness. The sample included children aged 2 to 16 years with a chronic PI and their aged-matched healthy siblings (n = 169 dyads). Physical-mental comorbidity (PM) was present if children screened positive for ≥1 mental illness on the Mini International Neuropsychiatric Interview for Children and Adolescents. Parents completed the Strengths and Difficulties Questionnaire (SDQ) to measure child and sibling mental health. Within child-sibling dyads, siblings of children with PI had significantly worse mental health related to conduct problems (d = 0.31), peer problems (d = 0.18) and total difficulties (d = 0.20). Siblings of children with PM had significantly better mental health related to emotional problems (d = 0.42), hyperactivity/inattention (d = 0.23) and total difficulties (d = 0.32). Siblings of children with PI had similar mental health compared with child population norms used in the development of the SDQ. In contrast, siblings of children with PM had significantly worse mental health across all SDQ domains, with the exception of prosocial behaviour. After adjusting for parent psychopathology and family functioning, no statistically significant differences between siblings of children with PM versus siblings of children with PI were found. Differences in mental health exist between children with PI or PM versus their healthy siblings. However, differences between siblings of children with PI versus siblings of children with PM can be explained by parental and family factors (e.g. marital status, education and income). Findings reinforce family-centred care approaches to address the needs of children with PI or PM and their families.

Generation of four iPSC lines from a family harboring a 1p36–35 haplotype linked with bipolar disorder and recurrent depressive disorder: Three-generation patients and a healthy sibling

Induced pluripotent stem cells (iPSCs) obtained from genetically characterized patients benefit the biological study of bipolar disorder (BD). Here, we present iPSC lines from three-generation patients with BD and recurrent depressive disorder (RDD) and a healthy control sibling in a family. All patients shared the specified haplotype in the 1p36–35, previously reported as the susceptibility locus of mood disorders. iPSCs were generated with the reprogramming factors OTC3/4, l-MYC, LIN28, SOX2, KLF4, and p53 shRNA through non-integrated episomal vectors. All iPSC lines strongly expressed pluripotency markers and proved the ability to differentiate into three germ lineages in vitro.

The Other Sibling: A Systematic Review of the Mental Health Effects on a Healthy Sibling of a Child With a Chronic Disease.

The Center for Disease Control and Prevention (CDC) defines chronic diseases broadly as conditions that last over one year and require ongoing medical attention or limit activities of daily living or both. The diagnosis of a child with a chronic disease affects parents' mental health and functioning, included in this are the siblings of this child. The impact on a sibling of a child with chronic disease involves higher risks of anxiety, depression, feelings of worry about the brother or sister's future, and social problems.Three databases search were performed, and 16 articles were assessed in this systematic review that complies with inclusion and exclusion criteria.The siblings of those with chronic illnesses have higher reported emotional, behavioral, and social problems than those with healthy siblings. More research and studies with control groups and larger samples could contribute to a better understanding of the long-term effects of having a sibling with a chronic disease.

High-Throughput Human Complement C3 N-Glycoprofiling Identifies Markers of Early Onset Type 1 Diabetes Mellitus in Children

Recently, it was shown that children at the onset of type 1 diabetes (T1D) have a higher proportion of oligomannose glycans in their total plasma protein N-glycome compared to their healthy siblings. The most abundant complement component, glycoprotein C3, contains two N-glycosylation sites occupied exclusively by this type of glycans. Furthermore, complement system, as well as C3, was previously associated with T1D. It is also known that changes in glycosylation can modulate inflammatory responses, so our aim was to characterize the glycosylation profile of C3 in T1D. For this purpose, we developed a novel high-throughput workflow for human C3 concanavalin A lectin affinity enrichment and subsequent LC-MS glycopeptide analysis which enables protein-specific N-glycosylation profiling. From the Danish Childhood Diabetes Register, plasma samples of 61 children/adolescents newly diagnosed with T1D and 84 of their unaffected siblings were C3 N-glycoprofiled. Significant changes of C3 N-glycan profiles were found. T1D was associated with an increase in the proportion of unprocessed glycan structures with more mannose units. A regression model including C3 N-glycans showed notable discriminative power between children with early onset T1D and their healthy siblings with area under curve of 0.879. This study confirmed our previous findings of plasma high-mannose glycan changes in a cohort of recent onset T1D cases, suggesting the involvement of C3 N-glycome in T1D development. Our C3 glycan-based discriminative model could be valuable in assessment of T1D risk in children.

Another Reason for Vaccine Hesitancy in Turkey: Siblings with Autism Spectrum Disorder

Despite studies showing no link between the measles-mumps-rubella vaccine and autism spectrum disorder (ASD), the belief that the vaccine causes autism can still affect parents' attitudes towards vaccines. This study aimed to investigate the vaccination status, vaccine information source, and the factors related to vaccine hesitancy diagnosed with ASD and their younger siblings based on interviews and questionnaires. A questionnaire was performed on 37 ASD groups (parents of children with ASD and their younger siblings) and 65 control groups (families with healthy children and healthy younger siblings). The research was conducted between 1st January 2019 and 31st December 2019. Incomplete vaccination was found higher in both children with ASD(n=37) and their younger siblings compared to the healthy control group(n=65) (p=0.045; p=0.016). The four children (10.8%) diagnosed with ASD had five siblings with incomplete or missing vaccinations. Families with children with ASD stated that their knowledge of vaccines was sufficient compared to the control group (p=0.021). All parents stated the autism vaccination relationship as the reason for incomplete vaccination. Parents of children with ASD may delay or reject vaccination for their children and their younger siblings.